Melatonin’s mechanisms in the battle against overweight

Overweight is looked upon as a global epidemic with grave consequences for public health. In a new review article that is published in International Journal of Molecular Sciences, scientists look closer at the relation between melatonin and overweight. Primarily known for its role as a sleep hormone, melatonin is also important for the body’s carbohydrate and lipid metabolism. The authors study melatonin’s role in the body’s energy metabolism and in oxidative stress and inflammation, which is known to make overweight bad for your health. They also look at how melatonin affects the circadian rhythm and its role in sleep disturbances and the gut flora that also influence body weight.

Around 30 percent of the global population (over two billion people) is believed to suffer from weight problems. Overweight and obesity are linked to a number of dysfunctions such as insulin resistance, elevated cholesterol levels, and hypertension, all of which are part of metabolic syndrome – the early stage of type 2 diabetes. Non-alcoholic fatty liver disease, chronic inflammation, cardiovascular disease, and cancer are also more prevalent among people who weigh too much. Overweight comes with a huge human and socioeconomic price tag that requires more insight and action if we are to bend the curve. It looks as if melatonin has a certain amount of potential in the fight against overweight for several reasons.

What is melatonin?

Melatonin is found in all living organisms – including bacteria. In humans, melatonin plays a major role in controlling the circadian rhythm (24-hour clock) that is responsible for regulating a variety of body functions.
We primarily produce melatonin in our pineal gland that is located right in the middle of our brain. Melatonin’s precursor is called serotonin and is also produced in the body, starting early in the morning as soon as we get exposed to “blue” daylight. At nightfall when it gets dark outside, the body converts serotonin into melatonin which makes us feel drowsy so we can sleep during the night.
Melatonin, essentially a hormone or a neurotransmitter, affects the majority of cells in the body. In addition, it is a powerful antioxidant that repairs cell damage while we are asleep. Altogether, melatonin affects our circadian rhythm, energy turnover, weight regulation, blood sugar, immune defense, anti-inflammatory response, cell protection, and even cancer protection.
Our endogenous melatonin synthesis decreases with age because the pineal gland calcifies. This contributes to our ageing process. In their new review article, the scientists look at melatonin’s different roles in connection with overweight through all the phases of life.

How melatonin affects overweight

Back in 1984, researchers (Bartness et al.) found that hamsters gained weight if they had their pineal gland removed. Ever since, science has assumed that there is a connection between the pineal gland, melatonin, and weight gain. Later, animal studies demonstrated that melatonin supplementation helped lower body weight, namely by reducing the dangerous white fat (abdominal fat) in animals that were fed a diet high in fat and carbohydrate.
Clinical studies of humans have shown varying results. According to a new meta-analysis of 23 studies, 11 of the studies documented that melatonin supplements had a significant impact on weight loss, BMI, and waist circumference when compared to placebo. Also, it appears that the melatonin dose and treatment period influenced the result. In studies where the participants got 8 mg of melatonin or more, the results were better than in studies with lower doses.

Lipid levels in the blood

Many overweight people have non-alcoholic fatty liver disease (NAFLD). Their liver produces far too much cholesterol and triglyceride – typically from fructose – and has literally turned into a “fat factory”. Older studies of overweight rats with diabetes have shown a positive relation between melatonin supplements, weight loss, and lipid profiles.
Epidemiological studies suggest that melatonin supplements have the potential to improve the lipid profile, thereby preventing cardiovascular disease. It is believed that melatonin may contribute to a healthier cholesterol balance by lowering levels of LDL cholesterol (that are often elevated in connection with overweight and metabolic syndrome.) All in all, it appears that melatonin helps improve the lipid balance because it increases the body’s turnover of dietary fat and carbohydrate.

Carbohydrate turnover and insulin resistance

Many people who are overweight develop insulin resistance which is also a part of metabolic syndrome and type 2 diabetes. Insulin resistance means that the cells’ ability to absorb glucose is impaired because the body is less sensitive to the insulin it produces. As a result of this, it becomes difficult to reach satiety. Excess calories in the bloodstream are stored as fat, typically the dangerous abdominal fat that forms around and in the between the vital organs. Insulin resistance is insidious and is typically a result of eating a diet with too many refined carbohydrates and too much omega-6 from plant oils.
Researchers have looked at how melatonin affects insulin resistance in fat tissue, pancreatic tissue, and muscle tissue. In overweight patients that took a melatonin supplement for 12 weeks there was a measurable decrease in their insulin resistance. This suggests that melatonin can improve carbohydrate metabolism by increasing the body’s insulin sensitivity. Elevated nocturnal melatonin levels during our sleep are therefore related to improved insulin quality. It may even be that healthy sleep in itself has a positive impact on our digestion and metabolism in general.

Melatonin’s effect on overweight and satiety

The authors behind the new review article look at many different studies of how melatonin affects overweight through a number of complex mechanisms in the white fat (that overweight people have too much of) and the brown fat (that generates heat). They go through melatonin’s complicated role in the liver, the pancreas, and the muscle mass that is crucial for carbohydrate and fat metabolism. They also look at how melatonin influences the satiety hormone called leptin. It actually turns out that many people with insulin resistance also have leptin resistance. This is a vicious cycle that increases both hunger and weight problems. Most of the body’s cells have melatonin receptors, suggesting that nearly all our tissues need melatonin to function normally day and night.

Childhood overweight

If the mother’s metabolism is somehow disrupted during her pregnancy, for example by insulin resistance, diabetes, or night shift work, it can increase her child’s risk of being overweight in the early part of its life. This is partly due to the fact that the mother’s pineal gland secretes less melatonin. On the other hand, the melatonin in breast milk may help the child avoid being overweight later in life.

Menopausal overweight

When women reach menopause and their sex hormone levels drop it may cause hot flushes and other types of discomfort. It is normally the lack of estrogen that explains why they feel hungrier and start to gain weight. However, it seems that the plummeting melatonin levels have an even more significant impact on the weight gain that women typically experience at this stage in life. Also, many women suffer from severe, hormone-related sleep disturbances which makes melatonin supplements highly relevant.

Day and night rhythm, sleep disturbances, and overweight

According to the astronomical day, it is best for us humans to be awake during the daytime where it is light outside and to sleep at night where it is dark. However, many people have managed to push the boundaries and have a lifestyle that throws their natural rhythm off balance. This may be because of shift work, night shifts, jet lag, and the massive exposure to blue light from device screens (smartphones, tablets etc.) late in the evening. When you expose yourself to artificial light before bedtime it inhibits the body’s melatonin synthesis which makes it difficult to fall asleep and reach the sleep stage that is characterized by dream activity.
It's commonly known that lack of sleep is related to overweight, reduced insulin sensitivity, and cardiovascular disease. It is also known that the need for fast carbs and stimulants increases when you are tired and don’t get enough sleep. This is why one tends to consume far too many (and the wrong kind of) calories during the day.
Multiple studies have shown that melatonin works as a natural sleep pill that compensates for the body’s deficiency in a natural way. Melatonin and healthy sleep both have positive effects on body weight by regulating metabolic processes during sleep and making it easier to stay off the empty calories when we are awake and rested.

Untimely hunger late at night

Women who overeat late at night may suffer from low or disrupted melatonin synthesis. This increases the production of the stress hormone cortisol and another hormone named ghrelin that triggers hunger. The hormonal imbalances cause a craving for calories late at night. If people have sleep disturbances and lack melatonin they may want to consider taking a supplement to prevent untimely hunger.

Oxidative stress, inflammation, and overweight

Overweight is often linked to oxidative stress, especially because the cells in the white tissue release a variety of proinflammatory cytokines. This triggers chronic, low-grade inflammation that generates large amounts of free radicals. The condition is dangerous for your health because the free radicals spread to other sites in the body and set off chain reactions in cells and tissues. It becomes a serious threat when the free radicals attack cholesterol and unsaturated fatty acids in the cell membranes. Oxidative stress and chronic low-grade inflammation set the stage for a host of different chronic ailments such as atherosclerosis, diabetes, Alzheimer’s disease, and cancer. Melatonin, due to its powerful antioxidant properties, has a mitigating effect on the harmful impact of free radicals.

Gut flora and overweight

Our digestive system is highly important for our general health and well-being. Interestingly, our digestion is most active during our sleep. The gut flora is vital for nutrient uptake, lactic acid production, and for a number of metabolic processes that control our weight. Scientists have found significant differences in the gut flora in overweight people and people of normal weight.
As mentioned earlier, most of our melatonin is made by the pineal gland but the gut flora also produces the substance. In fact, there are particularly many melatonin receptors in intestinal tissue. Apparently, melatonin contributes to the essential diversity of our gut flora. Studies have shown that melatonin supplements can improve the gut flora in connection with colitis caused by insomnia. The authors also mention that melatonin helps regulate the nutrient uptake, which is important for the body’s energy metabolism. A diet that is rich in fiber also contributes to the diversity of our gut flora.

Melatonin supplements

Melatonin supplements normally contain melatonin in the exact same form as the melatonin that the body produces. Melatonin is a safe and thoroughly tested product without notable side effects.
Melatonin should always be taken just before bedtime. Because melatonin induces naturel drowsiness, it may reduce the ability to drive, operate machinery, or engage in activities that require your full attention.
Melatonin is normally not recommended for children under the age of 12 years or pregnant and breastfeeding women, unless directed otherwise by a physician. The normal dose is 3 mg daily and should be taken 30-60 minutes before bedtime. Some studies have looked at doses as high as 10 mg.

Conclusion

To sum up, the review article states that melatonin has a positive impact on blood lipids, insulin resistance, and overweight. This is likely to be because of melatonin’s role in regulating processes that are relevant for the circadian rhythm, fat tissue, gut flora, oxidative stress, inflammation, sleep disturbances, etc. Not all studies show that melatonin has a positive effect on weight loss. Therefore, the authors call for larger studies, perhaps with increased melatonin doses and longer intervention periods. This may contribute to a better understanding of melatonin’s role in weight management.
In any case, it is important to get a good night’s sleep to support your digestion, especially because lack of sleep can trigger increased hunger the following day. In the long run, this can be damaging to your insulin sensitivity. Melatonin supplementation is a good idea if you generally have sleep issues and want to lose weight.

References:

Qingyun Guan etb al. Mechanism of melatonin in Obesity: A Review. International Journal of Molecular Sciences. 2022

Ewa Waleca-Kapica et al. Melatonin and Female Hormone Secretion in Postmenopausal Overweight Women. International Journal of Molecular Sciences. 2015

Jiménez-Aranda A et al. Melatonin induces browning of inguinal white adipose tissue in Zucker diabetic fatty rats. J Pin Res 2013 E pub ahead of print

Brown Fat Cell Discovery May Lead To Treatment of Obesity. Sci-news.com 2013